Prediction of intrahepatic covalently closed circular DNA levels in patients with resolved hepatitis B virus infection: Impact of serum antibody to hepatitis B core antigen titers

IF 3.9 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Sung Kwan Bae, Junichi Arita, Nobuhisa Akamatsu, Akihiko Ichida, Yujiro Nishioka, Akinori Miyata, Takuya Kawahara, Yoshinori Inagaki, Yoshikuni Kawaguchi, Junichi Kaneko, Sumihito Tamura, Yasuhito Tanaka, Hiroshi Yotsuyanagi, Kyoji Moriya, Kiyoshi Hasegawa
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Abstract

Aim

The correlation between intrahepatic covalently closed circular DNA (cccDNA) levels and serum hepatitis B virus (HBV) markers in patients with resolved HBV infection (hepatitis B surface antigen [HBsAg]-negative and antibody to hepatitis B core antigen [anti-HBc]-positive) is unclear. We therefore examined the utility of anti-HBc titers as a surrogate marker of intrahepatic cccDNA levels in patients with resolved HBV infections.

Methods

Among 1005 patients who underwent hepatectomy between 2010 and 2018, a retrospective review was performed in 114 patients (76 with resolved HBV infection and 38 HBsAg-positive) with frozen specimens of the background liver. Clinical, biochemical, and virological data, including intrahepatic cccDNA levels, were retrospectively evaluated. Intrahepatic cccDNA levels were measured using droplet digital polymerase chain reaction.

Results

Intrahepatic cccDNA levels positively correlated with serum HBsAg levels (r = 0.609, p < 0.001) and anti-HBc titers (r = 0.542, p < 0.001). An intrahepatic cccDNA level of 22.2 copies/μg was the optimal cut-off for HBsAg positivity, with a sensitivity of 86.8% and specificity of 89.5%. Of the 76 cases with resolved HBV infection, 8 had high levels of intrahepatic cccDNA (≥22.2 copies/μg). Multivariate analyses showed that anti-HBc ≥ 11.0 sample/cut-off (S/CO) was an independent risk factor for high intrahepatic cccDNA levels (odds ratio, 12.6; 95% confidence interval, 2.4–66.156; P = 0.003).

Conclusions

Anti-HBc titers were positively correlated with intrahepatic cccDNA levels. Even in patients with resolved HBV infection, anti-HBc ≥ 11.0 S/CO was considered to indicate high intrahepatic cccDNA levels, comparable to those in HBsAg-positive cases. In this group, careful monitoring is required during immunosuppressive therapy to prevent HBV reactivation.

Abstract Image

乙型肝炎病毒感染消退患者肝内共价闭合环状DNA水平的预测:血清乙型肝炎核心抗原抗体滴度的影响
目的探讨乙肝病毒感染患者肝内共价闭合环状DNA (cccDNA)水平与血清乙型肝炎病毒(HBV)标志物(乙型肝炎表面抗原[HBsAg]阴性和乙型肝炎核心抗原抗体[anti-HBc]阳性)的相关性。因此,我们研究了抗hbc滴度作为解决HBV感染患者肝内cccDNA水平的替代标记物的效用。方法对2010 - 2018年1005例肝切除术患者进行回顾性分析,其中114例患者(76例HBV感染消退,38例hbsag阳性)的冷冻背景肝标本进行回顾性分析。回顾性评估临床、生化和病毒学数据,包括肝内cccDNA水平。采用微滴数字聚合酶链反应检测肝内cccDNA水平。结果肝内cccDNA水平与血清HBsAg水平呈正相关(r = 0.609, p <;0.001)和抗hbc滴度(r = 0.542, p <;0.001)。肝内cccDNA水平为22.2拷贝/μg是HBsAg阳性的最佳临界值,敏感性为86.8%,特异性为89.5%。在76例HBV感染缓解的病例中,8例肝内cccDNA水平较高(≥22.2拷贝/μg)。多因素分析显示,抗hbc≥11.0样本/截止值(S/CO)是肝内cccDNA高水平的独立危险因素(优势比,12.6;95%置信区间为2.4-66.156;p = 0.003)。结论抗hbc滴度与肝内cccDNA水平呈正相关。即使在HBV感染解决的患者中,anti-HBc≥11.0 S/CO也被认为表明肝内cccDNA水平较高,与hbsag阳性病例相当。在该组中,在免疫抑制治疗期间需要仔细监测以防止HBV再激活。
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来源期刊
Hepatology Research
Hepatology Research 医学-胃肠肝病学
CiteScore
8.30
自引率
14.30%
发文量
124
审稿时长
1 months
期刊介绍: Hepatology Research (formerly International Hepatology Communications) is the official journal of the Japan Society of Hepatology, and publishes original articles, reviews and short comunications dealing with hepatology. Reviews or mini-reviews are especially welcomed from those areas within hepatology undergoing rapid changes. Short communications should contain concise definitive information.
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